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Background Treatment of thoracolumbar burst fractures has traditionally involved spinal instrumentation with fusion performed with standard open surgical techniques. Novel surgical strategies, including instrumentation without fusion and percutaneous instrumentation alone, have been considered less invasive and more efficient treatments. Objective To review the current literature and determine the role of fusion in instrumented fixation, as well as the role of percutaneous instrumentation, in the treatment of patients with thoracolumbar burst fractures. Methods The task force members identified search terms/parameters and a medical librarian implemented the literature search, consistent with the literature search protocol (see Appendix I), using the National Library of Medicine PubMed database and the Cochrane Library for the period from January 1, 1946 to March 31, 2015. Results A total of 906 articles were identified and 38 were selected for full-text review. Of these articles, 12 articles met criteria for inclusion in this systematic review. Conclusion There is grade A evidence for the omission of fusion in instrumented fixation for thoracolumbar burst fractures. There is grade B evidence that percutaneous instrumentation is as effective as open instrumentation for thoracolumbar burst fractures. Question Does the addition of arthrodesis to instrumented fixation improve outcomes in patients with thoracic and lumbar burst fractures? Recommendation It is recommended that in the surgical treatment of patients with thoracolumbar burst fractures, surgeons should understand that the addition of arthrodesis to instrumented stabilization has not been shown to impact clinical or radiological outcomes, and adds to increased blood loss and operative time. Strength of Recommendation: Grade A. Question How does the use of minimally invasive techniques (including percutaneous instrumentation) affect outcomes in patients undergoing surgery for thoracic and lumbar fractures compared to conventional open techniques? Recommendation Stabilization using both open and percutaneous pedicle screws may be considered in the treatment of thoracolumbar burst fractures as the evidence suggests equivalent clinical outcomes. Strength of Recommendation: Grade B The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_12.

Question 1 Are there classification systems for fractures of the thoracolumbar spine that have been shown to be internally valid and reliable (ie, do these instruments provide consistent information between different care providers)? Recommendation 1 A classification scheme that uses readily available clinical data (eg, computed tomography scans with or without magnetic resonance imaging) to convey injury morphology, such as Thoracolumbar Injury Classification and Severity Scale or the AO Spine Thoracolumbar Spine Injury Classification System, should be used to improve characterization of traumatic thoracolumbar injuries and communication among treating physicians. Strength of Recommendation: Grade B. Question 2 In treating patients with thoracolumbar fractures, does employing a formally tested classification system for treatment decision-making affect clinical outcomes? Recommendation 2 There is insufficient evidence to recommend a universal classification system or severity score that will readily guide treatment of all injury types and thereby affect outcomes. Strength of Recommendation: Grade Insufficient The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_2.

Question 1 Does routine screening for deep venous thrombosis prevent pulmonary embolism (or venous thromboembolism (VTE)-associated morbidity and mortality) in patients with thoracic and lumbar fractures? Recommendation 1 There is insufficient evidence to recommend for or against routine screening for deep venous thrombosis in preventing pulmonary embolism (or VTE-associated morbidity and mortality) in patients with thoracic and lumbar fractures. Strength of Recommendation: Grade Insufficient. Question 2 For patients with thoracic and lumbar fractures, is one regimen of VTE prophylaxis superior to others with respect to prevention of pulmonary embolism (or VTE-associated morbidity and mortality)? Recommendation 2 There is insufficient evidence to recommend a specific regimen of VTE prophylaxis to prevent pulmonary embolism (or VTE-associated morbidity and mortality) in patients with thoracic and lumbar fractures. Strength of Recommendation: Grade Insufficient. Question 3 Is there a specific treatment regimen for documented VTE that provides fewer complications than other treatments in patients with thoracic and lumbar fractures? Recommendation 3 There is insufficient evidence to recommend for or against a specific treatment regimen for documented VTE that would provide fewer complications than other treatments in patients with thoracic and lumbar fractures. Strength of Recommendation: Grade Insufficient. Recommendation 4 Based on published data from pooled (cervical and thoracolumbar) spinal cord injury populations, the use of thromboprophylaxis is recommended to reduce the risk of VTE events in patients with thoracic and lumbar fractures. Consensus Statement by the Workgroup The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_7.

Question 1 Does the surgical treatment of burst fractures of the thoracic and lumbar spine improve clinical outcomes compared to nonoperative treatment? Recommendation 1 There is conflicting evidence to recommend for or against the use of surgical intervention to improve clinical outcomes in patients with thoracolumbar burst fracture who are neurologically intact. Therefore, it is recommended that the discretion of the treating provider be used to determine if the presenting thoracic or lumbar burst fracture in the neurologically intact patient warrants surgical intervention. Strength of Recommendation: Grade Insufficient. Question 2 Does the surgical treatment of nonburst fractures of the thoracic and lumbar spine improve clinical outcomes compared to nonoperative treatment? Recommendation 2 There is insufficient evidence to recommend for or against the use of surgical intervention for nonburst thoracic or lumbar fractures. It is recommended that the decision to pursue surgery for such fractures be at the discretion of the treating physician. Strength of Recommendation: Grade Insufficient The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_1.

QUESTION Does early surgical intervention improve outcomes for patients with thoracic and lumbar fractures? RECOMMENDATIONS There is insufficient and conflicting evidence regarding the effect of timing of surgical intervention on neurological outcomes in patients with thoracic and lumbar fractures. Strength of Recommendation: Grade Insufficient It is suggested that "early" surgery be considered as an option in patients with thoracic and lumbar fractures to reduce length of stay and complications. The available literature has defined "early" surgery inconsistently, ranging from

QUESTION 1 Which neurological assessment tools have demonstrated internal reliability and validity in the management of patients with thoracic and lumbar fractures (ie, do these instruments provide consistent information between different care providers)? RECOMMENDATION 1 Numerous neurologic assessment scales (Functional Independence Measure, Sunnybrook Cord Injury Scale and Frankel Scale for Spinal Cord Injury) have demonstrated internal reliability and validity in the management of patients with thoracic and lumbar fractures. Unfortunately, other contemporaneous measurement scales (ie, American Spinal Cord Injury Association Impairment Scale) have not been specifically studied in patients with thoracic and lumbar fractures. Strength of Recommendation: Grade C. QUESTION 2 Are there any clinical findings (eg, presenting neurological grade/function) in patients with thoracic and lumbar fractures that can assist in predicting clinical outcomes? RECOMMENDATION 2 Entry American Spinal Injury Association Impairment Scale grade, sacral sensation, ankle spasticity, urethral and rectal sphincter function, and AbH motor function can be used to predict neurological function and outcome in patients with thoracic and lumbar fractures (Table I https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_4_table1). Strength of Recommendation: Grade B The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_4.

Question Does the choice of surgical approach (anterior, posterior, or combined anterior-posterior) improve clinical outcomes in patients with thoracic and lumbar fractures? Recommendations In the surgical treatment of patients with thoracolumbar burst fractures, physicians may use an anterior, posterior, or a combined approach as the selection of approach does not appear to impact clinical or neurological outcomes. Strength of Recommendation: Grade B With regard to radiologic outcomes in the surgical treatment of patients with thoracolumbar fractures, physicians may utilize an anterior, posterior, or combined approach because there is conflicting evidence in the comparison among approaches. Strength of Recommendation: Grade Insufficient With regard to complications in the surgical treatment of patients with thoracolumbar fractures, physicians may use an anterior, posterior, or combined approach because there is conflicting evidence in the comparison among approaches. Strength of Recommendation: Grade Insufficient The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_11.

Question Does the administration of a specific pharmacologic agent (eg, methylprednisolone) improve clinical outcomes in patients with thoracic and lumbar fractures and spinal cord injury? Recommendation There is insufficient evidence to make a recommendation; however, the task force concluded, in light of previously published data and guidelines, that the complication profile should be carefully considered when deciding on the administration of methylprednisolone. Strength of recommendation: Grade Insufficient The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_5.

Question Does the active maintenance of arterial blood pressure after injury affect clinical outcomes in patients with thoracic and lumbar fractures? Recommendations There is insufficient evidence to recommend for or against the use of active maintenance of arterial blood pressure after thoracolumbar spinal cord injury. Grade of Recommendation: Grade Insufficient However, in light of published data from pooled (cervical and thoracolumbar) spinal cord injury patient populations, clinicians may choose to maintain mean arterial blood pressures >85 mm Hg in an attempt to improve neurological outcomes. Consensus Statement by the Workgroup The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_6.

Background: Inadvertent hyperventilation is associated with poor outcomes from traumatic brain injury (TBI). Hypocapnic cerebral vasoconstriction is well described and causes an immediate and profound decrease in cerebral perfusion. The hemodynamic effects of positive-pressure ventilation (PPV) remain incompletely understood but may be equally important, particularly in the hypovolemic patient with TBI. Objective: Preliminary report on the application of a previously described mathematical model of perfusion and ventilation to prehospital data to predict intrathoracic pressure. Methods: Ventilation data from 108 TBI patients (76 ground transported, 32 helicopter transported) were used for this analysis. Ventilation rate (VR) and end-tidal carbon dioxide (PetCO2) values were used to estimate tidal volume (VT). The values for VR and estimated VT were then applied to a previously described mathematical model of perfusion and ventilation. This model allows input of various lung parameters to define a pressure–volume relationship, then derives mean intrathoracic pressure (MITP) for various VT and VR values. For this analysis, normal lung parameters were utilized. Separate analyses were performed assuming either fixed or variable PaCO2–PetCO2 differences. Ground and air medical patients were compared with regard to VR, PetCO2, estimated VT, and predicted MITP. Results: A total of 10,647 measurements were included from the 108 TBI patients, representing Received July 11, 2014 from the Department of Emergency Medicine, University of California at San Diego, La Jolla, California (DPD, SAA, GV, JVD), School of Medicine, University of California San Diego, La Jolla, California (KS), Division of Cardiology, University of California San Diego, La Jolla, California (RDH), Division of Cardiology, The Ohio State University, Columbus, Ohio (RDH), Department of Anesthesiology (AM) and Division of Pulmonary and Critical Care (RS), University of California at San Diego, La Jolla, California, and Rural/Metro Ambulance, San Diego, California, and San Diego Department of Fire–Rescue, San Diego, California (RF, CB, JVD). Accepted for publication August 4, 2014. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This paper was presented orally at the Resuscitation Science Symposium, 2011. Address correspondence to Steve A. Aguilar, MD, UC San Diego Emergency Medicine, 200 West Arbor Drive #8676, San Diego, CA 92103, USA. E-mail: SteveAguilarMD@gmail.com doi: 10.3109/10903127.2014.959228 about 13 minutes of ventilation per patient. Mean VR values were higher for ground patients versus air patients (21.6 vs. 19.7 breaths/min; p < 0.01). Estimated VT values were similar for ground and air patients (399 mL vs. 392 mL; p = NS) in the fixed model but not the variable (636 vs. 688 mL, respectively; p < 0.01). Mean PetCO2 values were lower for ground versus air patients (30.6 vs. 33.8 mmHg; p < 0.01). Predicted MITP values were higher for ground versus air patients, assuming either fixed (9.0 vs. 8.1 mmHg; p < 0.01) or variable (10.9 vs. 9.7 mmHg; p < 0.01) PaCO2–PetCO2 differences. Conclusions: Predicted MITP values increased with ventilation rates. Future studies to externally validate this model are warranted.

Options for people with severe paralysis who have lost the ability to communicate orally are limited. We describe a method for communication in a patient with late-stage amyotrophic lateral sclerosis (ALS), involving a fully implanted brain–computer interface that consists of subdural electrodes placed over the motor cortex and a transmitter placed subcutaneously in the left side of the thorax. By attempting to move the hand on the side opposite the implanted electrodes, the patient accurately and independently controlled a computer typing program 28 weeks after electrode placement, at the equivalent of two letters per minute. The brain–computer interface offered autonomous communication that supplemented and at times supplanted the patient’s eye-tracking device. (Funded by the Government of the Netherlands and the European Union; ClinicalTrials.gov number, NCT02224469.)

This second part of a comprehensive review of primary vertebral tumors focuses on locally aggressive and malignant tumors. As discussed in the earlier part of the review, both benign and malignant types of these tumors affect the adult and the pediatric population, and an understanding of their subtleties may increase their effective resection. In this review, we discuss the epidemiologic, histological, and imaging features of the most common locally aggressive primary vertebral tumors (chordoma and giant-cell tumor) and malignant tumors (chondrosarcoma, Ewing sarcoma, multiple myeloma or plasmacytoma, and osteosarcoma). The figures used for illustration are from operative patients of the senior authors (Z.L.G. and J.H.C.). Taken together, parts 1 and 2 of this article provide a thorough and illustrative review of primary vertebral tumors.

BACKGROUND There are currently no satisfactory treatments or experimental models showing autonomic dysfunction for intramedullary spinal cord gliomas (ISCG). OBJECTIVE To develop a rat model of ISCG and investigate whether genetically engineered human neural stem cells (F3.hNSCs) could be developed into effective therapies for ISCG. METHODS Immunodeficient/Rowett Nude rats received C6 implantation of G55 human glioblastoma cells (10K/each). F3.hNSCs engineered to express either cytosine deaminase gene only (i.e., F3.CD) or dual genes of CD and thymidine kinase (i.e., F3.CD-TK) converted benign 5-fluorocytosine and ganciclovir into oncolytic 5-fluorouracil and ganciclovir-triphosphate, respectively. ISCG rats received injection of F3.CD-TK, F3.CD, or F3.CD-TK debris near the tumor epicenter 7 days after G55 seeding, followed with 5-FC (500 mg/kg/5 mL) and ganciclovir administrations (25 mg/kg/1 mL/day × 5/each repeat, intraperitoneal injection). Per humane standards for animals, loss of weight-bearing stepping in the hindlimb was used to determine post-tumor survival. Also evaluated were autonomic functions and tumor growth rate in vivo. RESULTS ISCG rats with F3.CD-TK treatment survived significantly longer (37.5 ± 4.78 days) than those receiving F3.CD (21.5 ± 1.75 days) or F3.CD-TK debris (19.3 ± 0.85 days; n = 4/group; P < .05, median rank test), with significantly improved autonomic function and reduced tumor growth rate. F3.DC-TK cells migrated diffusively into ISCG clusters to mediate oncolytic effect. CONCLUSION Dual gene-engineered human neural stem cell regimen markedly prolonged survival in a rat model that emulates somatomotor and autonomic dysfunctions of human cervical ISCG. F3.CD-TK may provide a novel approach to treating clinical ISCG. ABBREVIATIONS 5FC, 5-fluorocytosineBBB, Basso, Beattie, and BresnahanCD, cytosine deaminaseDP, diastolic blood pressureGCV, ganciclovir; hNSCs, human neural stem cellsISCG, intramedullary spinal cord gliomasMAP, mean arterial blood pressureNSCs, neural stem cellsSP, systolic blood pressureTK, thymidine kinase.

Spinal cord injury (SCI) at high spinal levels (e.g., above thoracic level 5) causes systemic immune suppression; however, the underlying mechanisms are unknown. Here, we show that profound plasticity develops within spinal autonomic circuitry below the injury, creating a sympathetic anti-inflammatory reflex, and that chemogenetic silencing of this reflex circuitry blocks post-SCI immune suppression. These data provide new insights and potential therapeutic options for limiting the devastating consequences of post-traumatic autonomic hyperreflexia and post-injury immune suppression.

OBJECTIVE: Acquired immunity has been demonstrated in Fischer rats bearing syngeneic 9L tumors after herpes simplex virus (HSV) thymidine kinase (TK) gene transfection and ganciclovir treatment. The nature of this immunity in rats and its relevance to the HSV TK/ganciclovir protocol for human subjects remain to be determined. In this study, levels of major histocompatibility complex (MHC) Class I and II antigen expression were measured before and after HSV TK transfection, in an effort to document immunomodulatory changes caused by gene therapy. METHODS: Tumor cells from the 9L gliosarcoma cell line, three primary human glioma cultures, and the human glioma cell line U87 MG were transduced with HSV TK vector-containing supernatant from fibroblast-producing cells (titer of 5 x 10 6 colony-forming units/ml) and selected in G418 medium for neomycin resistance. Clones were pooled or individually selected for cell-killing assays with ganciclovir, to confirm TK expression (10 3 cells/well in a 96-well dish). Northern analyses using MHC Class I and Class II complementary deoxyribonucleic acid probes were performed on blots containing total ribonucleic acid from wild-type tumor cells and HSV TK transfectants. A β-actin complementary deoxyribonucleic acid probe served as an internal control. Cell surface expression was confirmed with flow cytometry. The induction of MHC Class I was tested for cycloheximide and genistein sensitivity. RESULTS: All cell cultures exhibited increases in MHC Class I but not MHC Class II expression, as determined by Northern analysis densitometry and flow cytometry. Cycloheximide treatment did not diminish the up-regulation of MHC Class I after retroviral transfection, implicating a signal transduction pathway that does not require ongoing protein synthesis. Genistein pretreatment of cell cultures did diminish the up-regulation of MHC Class I, implicating a tyrosine kinase in the signaling cascade. CONCLUSION: Induction of MHC Class I in rat and human glioma cells after HSV TK retroviral gene therapy is a primary effect that is dependent on tyrosine kinase activity. Specific immune responses generated after transfection may represent an important general side effect of gene therapy protocols. Elucidation of the mechanism of immunomodulation after gene therapy will likely yield safer and more effective clinical protocols.

Primary vertebral tumors, although less common than metastases to the spine, make up a heterogeneous group of neoplasms that can pose diagnostic and treatment challenges. They affect both the adult and the pediatric population and may be benign, locally aggressive, or malignant. An understanding of typical imaging findings will aid in accurate diagnosis and help neurosurgeons appreciate anatomic subtleties that may increase their effective resection. An understanding of the histological similarities and differences between these tumors is imperative for all members of the clinical team caring for these patients. In this first review of 2 parts, we discuss the epidemiological, histological, and imaging features of the most common benign primary vertebral tumors-aneurysmal bone cyst, chondroma and enchondroma, hemangioma, osteoid osteoma, and osteoblastoma-and lesions related to eosinophilic granuloma and fibrous dysplasia. In addition, we discuss the basic management paradigms for each of these diagnoses. In combination with part II of the review, which focuses on locally aggressive and malignant tumors, this article provides a comprehensive review of primary vertebral tumors.

OBJECTIVE: Meningiomas of the anterior cranial base can be approached with a variety of techniques. The extended bifrontal approach is often thought to be associated with increased morbidity because of the need for extensive removal of the bone and longer surgical times. The authors have attempted to quantitate retraction-related edema occurring after surgery to determine whether the extra bone removal limits retraction and reduces the chance of brain injury. METHODS: Charts were reviewed for patients who underwent extended bifrontal craniotomies performed for meningiomas at the University of California, San Francisco, between 1997 and 2005. Magnetic resonance imaging scans obtained before and after surgery were reviewed for brain edema as indicated by fluid-attenuated inversion recovery/T2 abnormality and grouped into four categories: A, no edema; B, edema restricted to the gyrus rectus; C, edema beyond the gyrus rectus; and D, extensive bifrontal edema. RESULTS: Forty-five patients were identified. Fifty-four percent of patients had tumors with a diameter of more than 4 cm. Simpson Grade 2 or 3 resection was achieved in 82% of patients, and the average operative time was 12.3 hours. Vision outcome was favorable in 74% of patients. Extent of fluid-attenuated inversion recovery abnormality remained unchanged in 87.5%, with 91% of patients in categories A or B edema remaining in those categories after surgery. There were no infections and there were two cerebrospinal fluid leaks. CONCLUSION: The extended bifrontal approach is a safe surgical procedure with limited morbidity that the authors think: 1) prevents secondary brain injury from excessive retraction; 2) offers great flexibility of view for the surgeon; and 3) should be considered the preferred approach compared with the standard bifrontal craniotomy for large tumors of the anterior cranial base.